rs748995403

Variant names:

• chr1-36088910-CGCAGCGGCGATGGCG-C
• rs748995403
• NM_017825.3:c.15_29delGATGGCGGCAGCGGC

Your query was ambiguous. Multiple possible variants found:

• chr1-36088910-CGCAGCGGCGATGGCG-C
• chr1-36088910-CGCAGCGGCGATGGCG-CGCAGCGGCGATGGCGGCAGCGGCGATGGCG

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_017825.3(ADPRS):​c.15_29delGATGGCGGCAGCGGC​(p.Met6_Ala10del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000146 in 1,372,712 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: ADPRS NM_017825.3 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.95
• Publications: 0 publications found

Genes affected

ADPRS (HGNC:21304): (ADP-ribosylserine hydrolase) This gene encodes a member of the ADP-ribosylglycohydrolase family. The encoded enzyme catalyzes the removal of ADP-ribose from ADP-ribosylated proteins. This enzyme localizes to the mitochondria, in addition to the nucleus and cytoplasm.[provided by RefSeq, Feb 2009]

ADPRS Gene-Disease associations (from GenCC):

• neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_017825.3

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017825.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADPRS	NM_017825.3	MANE Select	c.15_29delGATGGCGGCAGCGGC	p.Met6_Ala10del	disruptive_inframe_deletion	Exon 1 of 6	NP_060295.1	Q9NX46

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADPRS	ENST00000373178.5	TSL:1 MANE Select	c.15_29delGATGGCGGCAGCGGC	p.Met6_Ala10del	disruptive_inframe_deletion	Exon 1 of 6	ENSP00000362273.4	Q9NX46
	ADPRS	ENST00000896939.1		c.15_29delGATGGCGGCAGCGGC	p.Met6_Ala10del	disruptive_inframe_deletion	Exon 1 of 6	ENSP00000566998.1
	ADPRS	ENST00000932449.1		c.15_29delGATGGCGGCAGCGGC	p.Met6_Ala10del	disruptive_inframe_deletion	Exon 1 of 6	ENSP00000602508.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000146 AC: 2 AN: 1372712 Hom.: 0 AF XY: 0.00000148 AC XY: 1 AN XY: 677646

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000345 AC: 1 AN: 28954

American (AMR) AF: 0.00 AC: 0 AN: 34872

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24544

East Asian (EAS) AF: 0.00 AC: 0 AN: 33776

South Asian (SAS) AF: 0.0000127 AC: 1 AN: 78656

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36766

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4240

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1073744

Other (OTH) AF: 0.00 AC: 0 AN: 57160

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0385499), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs748995403; hg19: chr1-36554511;